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研究揭示一千种肿瘤的转录性瘤内异质性标志
2023-06-07 17:01

以色列魏茨曼科学研究所Itay Tirosh小组揭示一千种肿瘤的转录性瘤内异质性标志。相关论文于2023年5月31日在线发表于国际学术期刊《自然》上。

研究人员对77项不同研究的数据进行了整理、注释和整合,揭示了涵盖24种肿瘤类型的1163个肿瘤样本的转录瘤内异质性(ITH)的模式。在恶性细胞中,研究人员确定了41个一致的元程序,每个程序由几十个基因组成,这些基因在许多肿瘤的细胞亚群中协调地上调。这些元程序涵盖了不同的细胞过程,包括通用的(如细胞周期和压力)和特定的细胞系模式,研究人员将其映射为11个转录ITH的标志。癌细胞的大多数元程序与非恶性上皮细胞中的元程序相似,这表明很大一部分恶性ITH程序甚至在肿瘤发生之前就已经是可变的,反映了其起源细胞的生物学特性。

研究人员进一步将元程序分析扩展到六种常见的非恶性细胞类型,并利用它们来绘制肿瘤微环境中的细胞-细胞相互作用。总之,研究人员收集了一个全面的泛癌症单细胞RNA测序数据集,该数据集可通过Curated Cancer Cell Atlas网站获得,并利用该数据集对转录ITH进行了系统化的描述。

据介绍,每个肿瘤都包含不同的细胞状态,这些细胞状态是ITH的基础,是癌症治疗的核心挑战。最近有几十项研究开始通过单细胞RNA测序来描述ITH,但每项研究通常只对少数肿瘤进行分析,并对转录性ITH提供了一个狭隘的观点。

附:英文原文

Title: Hallmarks of transcriptional intratumour heterogeneity across a thousand tumours

Author: Gavish, Avishai, Tyler, Michael, Greenwald, Alissa C., Hoefflin, Rouven, Simkin, Dor, Tschernichovsky, Roi, Galili Darnell, Noam, Somech, Einav, Barbolin, Chaya, Antman, Tomer, Kovarsky, Daniel, Barrett, Thomas, Gonzalez Castro, L. Nicolas, Halder, Debdatta, Chanoch-Myers, Rony, Laffy, Julie, Mints, Michael, Wider, Adi, Tal, Rotem, Spitzer, Avishay, Hara, Toshiro, Raitses-Gurevich, Maria, Stossel, Chani, Golan, Talia, Tirosh, Amit, Suv, Mario L., Puram, Sidharth V., Tirosh, Itay

Issue&Volume: 2023-05-31

Abstract: Each tumour contains diverse cellular states that underlie intratumour heterogeneity (ITH), a central challenge of cancer therapeutics1. Dozens of recent studies have begun to describe ITH by single-cell RNA sequencing, but each study typically profiled only a small number of tumours and provided a narrow view of transcriptional ITH2. Here we curate, annotate and integrate the data from 77 different studies to reveal the patterns of transcriptional ITH across 1,163 tumour samples covering 24 tumour types. Among the malignant cells, we identify 41 consensus meta-programs, each consisting of dozens of genes that are coordinately upregulated in subpopulations of cells within many tumours. The meta-programs cover diverse cellular processes including both generic (for example, cell cycle and stress) and lineage-specific patterns that we map into 11 hallmarks of transcriptional ITH. Most meta-programs of carcinoma cells are similar to those identified in non-malignant epithelial cells, suggesting that a large fraction of malignant ITH programs are variable even before oncogenesis, reflecting the biology of their cell of origin. We further extended the meta-program analysis to six common non-malignant cell types and utilize these to map cell–cell interactions within the tumour microenvironment. In summary, we have assembled a comprehensive pan-cancer single-cell RNA-sequencing dataset, which is available through the Curated Cancer Cell Atlas website, and leveraged this dataset to carry out a systematic characterization of transcriptional ITH.

DOI: 10.1038/s41586-023-06130-4

Source: https://www.nature.com/articles/s41586-023-06130-4

Nature:《自然》,创刊于1869年。隶属于施普林格·自然出版集团,最新IF:69.504
官方网址:http://www.nature.com/
投稿链接:http://www.nature.com/authors/submit_manuscript.html


本期文章:《自然》:Online/在线发表

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